Enhanced expression of Lp-PLA2 and lysophosphatidylcholine in symptomatic carotid atherosclerotic plaques

Enhanced expression of Lp-PLA2 and lysophosphatidylcholine in symptomatic carotid atherosclerotic plaques
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DOI:
10.1161/strokeaha.107.503193
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发表时间:
2008-05-01
期刊:
影响因子:
8.3
通讯作者:
Lerman, Amir
Lerman, Amir
中科院分区:
医学1区
文献类型:
--
作者:
Mannheim, Dallit;Herrmann, Joerg;Lerman, Amir

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背景和目的循环脂蛋白相关磷脂酶 A(2) (Lp-PLA(2)) 已成为心血管疾病的新型生物标志物。然而,Lp-PLA(2) 斑块表达与斑块氧化应激、炎症和稳定性以及临床表现之间的相关性仍不清楚,特别是对于脑血管疾病。因此,本研究旨在检验接受颈动脉内膜切除术的患者有症状颈动脉斑块中Lp-PLA(2)表达高于无症状颈动脉斑块的假设。方法-通过免疫印迹和免疫染色测定167例颈动脉斑块中Lp-PLA(2)的表达。通过 NAD(P)H 氧化酶 p67phox 和 MMP-2 免疫印迹、氧化 LDL (oxLDL) 免疫反应性、巨噬细胞和天狼星红胶原染色来量化斑块氧化应激、炎症和稳定性。使用液相色谱串联质谱法测量 55 个斑块中的溶血磷脂酰胆碱 16:0 (lysoPC) 浓度。结果 - 有症状患者的斑块中 Lp-PLA(2) 表达显着高于无症状患者(1.66 +/- 0.19 与 1.14 +/- 0.10,P < 0.05),并且主要分布于肩部和坏死的脂质核心区域。与 oxLDL 和巨噬细胞含量共定位。同样,Lp-PLA2 表达与胶原蛋白含量相关,有症状患者的斑块中的胶原蛋白含量低于无症状患者的斑块(染色/视野的 9.1 +/- 2.2 与 18.5 +/- 1.7%,P < 0.001)。有症状患者斑块中的 LysoPC 斑块浓度显着高于无症状患者(437.0 +/- 57.91 与 228.84 +/- 37.00 mmol/L,P
Background and Purpose-Circulating lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) has emerged as a novel biomarker for cardiovascular diseases. However, the correlation between the plaque expression of Lp-PLA(2) and plaque oxidative stress, inflammation, and stability as well as the clinical presentation remains poorly defined, especially for cerebrovascular disease. Therefore, this study was performed to test the hypothesis that Lp-PLA(2) expression is higher in symptomatic than in asymptomatic carotid plaques of patients undergoing carotid endarterectomy.Methods-The expression of Lp-PLA(2) in 167 carotid artery plaques was determined by immunoblotting and immunostaining. Plaque oxidative stress, inflammation, and stability were quantified by NAD(P)H oxidase p67phox and MMP-2 immunoblotting, oxidized LDL (oxLDL) immunoreactivity, macrophage and Sirius red collagen staining. Lysophosphatidylcholine 16: 0 (lysoPC) concentration was measured in 55 plaques using liquid chromatography tandem mass spectrometry.Results-Lp-PLA(2) expression was significantly higher in plaques of symptomatic patients than asymptomatic patients (1.66 +/- 0.19 versus 1.14 +/- 0.10, P < 0.05) and localized mainly to shoulder and necrotic lipid core areas in colocalization with oxLDL and macrophage content. Similarly, Lp-PLA2 expression was related to collagen content, which was lower in plaques from symptomatic patients than in plaques from asymptomatic patients (9.1 +/- 2.2 versus 18.5 +/- 1.7% of staining/field, P < 0.001). LysoPC plaque concentration was significantly higher in plaques of symptomatic than asymptomatic patients (437.0 +/- 57.91 versus 228.84 +/- 37.00 mmol/L, P